Recurrent Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
PD-1 inhibitor, Randomized Controlled Trial, Neoadjuvant Chemoimmunotherapy, Head and Neck Squamous Cell Carcinoma, Locally Recurrent Disease
Brief summary
The goal of this clinical trial is to determine whether a perioperative PD-1 antibody-based treatment strategy, consisting of neoadjuvant PD-1 antibody plus chemotherapy followed by adjuvant PD-1 antibody after surgery, improves outcomes compared with the current standard treatment in patients with resectable locally recurrent head and neck squamous cell carcinoma (HNSCC). The study will also evaluate the safety of this perioperative treatment approach. The main questions it aims to answer are: Does perioperative PD-1 antibody-based therapy improve event-free survival compared with the current standard treatment? What adverse events occur during treatment with neoadjuvant PD-1 antibody plus chemotherapy and adjuvant PD-1 antibody? Researchers will compare a perioperative PD-1 antibody-based treatment strategy with the current standard treatment to determine which approach provides better clinical outcomes. Participants will: Be randomly assigned to one of two study groups. Receive either neoadjuvant PD-1 antibody plus chemotherapy followed by surgery and adjuvant PD-1 antibody, or undergo upfront surgery followed by standard postoperative treatment as indicated. Visit the clinic regularly for physical examinations, blood tests, imaging assessments, and other study procedures. Be followed after treatment to monitor disease status, treatment response, survival outcomes, and adverse events.
Interventions
DRUGNeoadjuvant PD-1 antibody plus chemotherapy
Administered once every 3 weeks for 2 to 4 cycles before surgery
PROCEDUREsurgery
Surgery followed by postoperative radiotherapy or chemoradiotherapy as clinically indicated.
DRUGAdjuvant PD-1 antibody
Administered postoperatively every 3 weeks for up to 15 cycles.
Sponsors
Yanjie Zhang, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 18 to 80 years old (inclusive). 2. Primary Tumor: Histologically or cytologically confirmed head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma). Patients must have previously received surgery and/or radiotherapy. 3. Diagnosis: Locally recurrent or metastatic disease confirmed by pathology and/or imaging. 4. Clinical Stage: T1-4a, N0-2, M0 (AJCC TNM Staging System, 8th Edition), with no evidence of distant metastasis, and the recurrent lesion is assessed as surgically resectable. 5. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Life Expectancy: Expected survival ≥ 6 months. 7. Immunotherapy: No significant contraindications to immunotherapy. 8. Consent to Surgery: Willing to undergo surgical treatment. 9. Adequate Organ Function: Hematology (without transfusion or hematopoietic growth factor support within 14 days): WBC ≥ 4.0 × 10⁹/L, ANC ≥ 1.5 × 10⁹/L, Platelets ≥ 100 × 10⁹/L, Hemoglobin ≥ 90 g/L. Biochemistry: Serum albumin ≥ 3.0 g/dL (30 g/L), Total bilirubin (TBIL) ≤ 1.5 × ULN, ALT and AST ≤ 2.5 × ULN, BUN and Creatinine ≤ 1.5 × ULN, or calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula). Coagulation: Adequate coagulation function defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN. For participants receiving anticoagulant therapy, PT must be within the intended therapeutic range of the anticoagulant. 10. Contraception: Female participants of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and must agree to use effective contraception during the study and for 6 months after the last dose of the anti-PD-1 antibody. Male participants with female partners of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose of the anti-PD-1 antibody. 11. Informed Consent: The participant must voluntarily join the study, sign the informed consent form, be compliant, and be willing to cooperate with follow-up.
Exclusion criteria
1. Prior treatment with anti-PD-1/PD-L1 antibodies, anti-PD-L2 antibodies, anti-CD137 antibodies, CTLA-4 antibodies, or other drugs/antibodies targeting T-cell co-stimulation or checkpoint pathways. 2. Presence of active severe autoimmune disease. Participants with conditions that are stable and do not require systemic immunosuppressive therapy are eligible, such as: Type I diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, and alopecia). 3. Has a congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10⁴ copies/mL), or active hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the assay). 4. Known allergy to the study drug or any of its excipients; or a history of severe allergic reactions to other monoclonal antibodies. 5. Occurrence of any of the following within 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, cardiac insufficiency of NYHA Class 2 or higher, clinically significant supraventricular or ventricular arrhythmias, or symptomatic congestive heart failure. 6. Vaccination with a live vaccine within 4 weeks prior to the first dose of the study drug. Inactivated virus vaccines for seasonal influenza administered via injection are permitted; however, intranasal live attenuated influenza vaccines are not permitted. 7. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 8. Known history of psychoactive substance abuse or drug addiction. 9. Pregnant or breastfeeding women. 10. Diagnosis of any other malignancy within 5 years prior to study entry, with the exception of locally treated and cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma in situ of the breast, and papillary thyroid cancer. 11. Presence of any other severe physical or mental illness or laboratory abnormality that may increase the risk of participating in the study, interfere with the study results, or render the participant unsuitable for participation in the study, as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | 2 years after randomization | Event-free survival (EFS) is defined as the time from randomization to the first occurrence of disease recurrence or metastasis after surgery; disease progression according to RECIST version 1.1 that prevents definitive surgery during preoperative treatment or occurs in participants who do not undergo definitive surgery; a second primary malignancy; or death from any cause. Disease progression during preoperative treatment that does not prevent definitive surgery is not considered an EFS event. Failure to undergo definitive surgery for reasons other than disease progression is not itself considered an EFS event. Participants without an EFS event will be censored at the date of the last adequate disease assessment. EFS will be estimated using the Kaplan-Meier method. The planned primary EFS analysis will be performed after all participants have had the opportunity for at least 24 months of follow-up after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 2 years after randomization | Overall survival (OS) is defined as the time from randomization to death from any cause. Participants without a documented death will be censored at the date they were last known to be alive. OS will be estimated using the Kaplan-Meier method. The planned primary OS analysis will be performed after all participants have had the opportunity for at least 24 months of follow-up after randomization. |
| 5-Year Event-Free Survival (EFS) | 5 years after randomization | Event-free survival (EFS) is defined as the time from randomization to the first occurrence of disease recurrence or metastasis after surgery; disease progression according to RECIST version 1.1 that prevents definitive surgery during preoperative treatment or occurs in participants who do not undergo definitive surgery; a second primary malignancy; or death from any cause. Disease progression during preoperative treatment that does not prevent definitive surgery is not considered an EFS event. Failure to undergo definitive surgery for reasons other than disease progression is not itself considered an EFS event. Participants without an EFS event will be censored at the date of the last adequate disease assessment or at 5 years after randomization, whichever occurs first. EFS will be estimated using the Kaplan-Meier method. |
| 5-Year Overall Survival (OS) | 5 years after randomization | Overall survival (OS) is defined as the time from randomization to death from any cause. Participants without a documented death will be censored at the date they were last known to be alive or at 5 years after randomization, whichever occurs first. OS will be estimated using the Kaplan-Meier method. |
| Adverse Events and Serious Adverse Events | From initiation of assigned treatment through 30 days after treatment completion or discontinuation; serious adverse events and adverse events of special interest through 90 days after treatment completion or discontinuation. | The number and percentage of participants with adverse events and serious adverse events will be summarized. Events will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Summaries will include event type, incidence, severity, onset and resolution dates, seriousness, relationship to study treatment, and outcome. |
| Pathologic Complete Response (pCR) Rate | Within 2 weeks after surgery | The percentage of participants receiving neoadjuvant treatment who undergo surgery and have no residual viable tumor cells in either the resected primary tumor or any sampled regional lymph node, corresponding to ypT0N0, based on postoperative pathological assessment. |
| Major Pathologic Response (MPR) Rate | Within 2 weeks after surgery | The percentage of participants receiving neoadjuvant treatment who undergo surgery and have 10% or less residual viable tumor in the resected specimen. MPR is defined as a residual viable tumor area divided by the total tumor bed area of 10% or less, as determined by blinded review by the pathology review committee. |
| Objective Response Rate (ORR) | At the preoperative tumor assessment after completion of 2 to 4 cycles of neoadjuvant treatment (each cycle is 21 days; approximately 6 to 12 weeks after initiation of neoadjuvant treatment). | The percentage of participants receiving neoadjuvant treatment who achieve a best overall radiographic response of complete response or partial response, as assessed according to Response Evaluation Criteria in Solid Tumors, version 1.1. |
Contacts
CONTACTYanjie Zhang, Doctor of Medicine
Outcome results
None listed